A new method for the analysis of cohort studies: implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure.

Implications of the multistage theory of carcinogenesis for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different patterns of excess risk related to duration of exposure, age at initial exposure, and follow-up time since exposure stopped, depending upon which stage of the carcinogenic process is affected by the carcinogen, i.e., action at an early stage or a late stage. New statistical methodologies are proposed to examine these patterns and are applied to the lung cancer mortality experience from a cohort study of smelter workers exposed to arsenic. Under this multistage hypothesis, the results indicate that arsenic exerts a definite late stage effect though an additional effect at the initial stage cannot be ruled out. The possibilities of biased conclusions resulting from incomplete exposure histories and lack of smoking information are also discussed as well as implications of these results to experimental animal studies.